N-arylamines compounds are important substructures in natural products and industrial chemicals, such as pharmaceuticals, dyes, and agricultural products. N-arylamines are useful for screening for pharmaceutical and biological activity and in the preparation of commercial polymers. It would be advantageous to prepare N-arylamine compounds from arylating compounds such as aryl halides and/or aryl tosylates because aryl halides are generally inexpensive and readily available, while aryl tosylates are easily prepared from phenols. However, to date, methods of producing N-arylamines are inefficient or economically unattractive. Many known processes that generate an aryl-nitrogen bond must be performed under harsh reaction conditions, or must employ activated substrates which are sometimes not available. Examples of procedures that generate aryl amine compounds include nucleophilic substitution of aryl precursors and synthesis of aryl amines via copper-mediated Uhlmann condensation reactions.
The commercialization of metallocene polyolefin catalysts has led to widespread interest in the design and preparation of other catalysts and catalyst systems, particularly for use in economical gas and slurry phase processes. Anionic, multidentate heteroatom ligands have received attention in polyolefins catalysis. Notable classes of bidentate anionic ligands which form active polymerization catalysts include N—N− and N—O− ligand sets. Examples of these types of catalysts include amidopyridines and polyolefin catalysts based on hydroxyquinolines.
U.S. Pat. No. 5,576,460 (the '460 patent) discloses two synthesis routes to preparing arylamine compounds. The first route includes reaction of a metal amide comprising a metal selected from the group consisting of tin, boron, zinc, magnesium, indium and silicon, with an aromatic compound comprising an activated substituent in the presence of a transition metal catalyst to form an arylamine. The second route utilizes an amine rather than a metal amide. The '460 patent teaches that this reaction be conducted at a temperature of less than about 120° C. and is drawn to the use of the arylamine as an intermediate in pharmaceutical and agricultural applications.
U.S. Pat. No. 5,929,281 discloses the preparation of heterocyclic aromatic amines in the presence of a catalyst system comprising a palladium compound and a tertiary phosphine and the preparation of arylamines in the presence of a catalyst system comprising a palladium compound and a trialkylphosphine.
U.S. Pat. No. 3,914,311 discloses a low temperature method of preparing an arylamine by the reaction of an amine with an aromatic compound having a displaceable activated substituent at temperatures as low as 25° C. in the presence of nickel catalyst and a base.
Other patents discussing N-arylamine compounds may include U.S. Pat. Nos. 6,235,938 and 6,518,444, among others, as well as references such as, Shen, Q., Shekhar, S, Stambuli, J. P., Hartwig, J. F., Angew. Chem., Int. Ed.; 2005, 44, 1371-1375.
A need exists for a general and efficient process of synthesizing N-arylamine compounds from readily available arylating compounds. The discovery and implementation of such a method would simplify the preparation of commercially significant organic N-aryl amines and would enhance the development of novel polymers and pharmacologically active compounds.